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肝细胞线粒体自噬在非酒精性脂肪性肝病发病机制中的作用

周振华 王灵台 高月求

引用本文:
Citation:

肝细胞线粒体自噬在非酒精性脂肪性肝病发病机制中的作用

DOI: 10.3969/j.issn.1001-5256.2019.12.036
基金项目: 

国家自然科学基金项目(81774268); 上海市科技创新行动计划临床医学领域项目(19401972500); 上海市卫生和计划生育委员会卫生行业临床研究专项计划(201840012); 

详细信息
  • 中图分类号: R575.5

Role of hepatocyte mitophagy in the pathogenesis of nonalcoholic fatty liver disease

Research funding: 

 

  • 摘要: 非酒精性脂肪性肝病已成为我国第一大慢性肝病和健康体检肝生化指标异常的首要原因。线粒体自噬可降解肝脏中功能受损的线粒体和错误折叠蛋白以调节细胞死亡,同时具有维持肝脏脂质代谢稳态的作用。脂肪组织分泌的脂联素与脂联素受体2结合,可增加肝脏Kupffer细胞分泌自噬激动剂,诱导肝细胞线粒体自噬,促进脂质代谢,从而减轻肝脏炎症,为研发疗效显著和机制明确的非酒精性脂肪性肝病治疗药物提供了新思路。

     

  • [1] RINELLA ME. Nonalcoholic fatty liver disease:A systematic review[J]. JAMA,2015,313(22):2263-2273.
    [2] DIEHL AM,DAY C. Cause,pathogenesis,and treatment of nonalcoholic steatohepatitis[J]. N Engl J Med,2017,377(21):2063-2072.
    [3] WEI GC,HE JY. Traditional Chinese medicine intervention to nonalcoholic fatty liver disease based on physique identification[J]. J Changchun Univ Chin Med,2018,34(3):518-521.(in Chinese)魏功昌,何瑾瑜.中医体质辨识治疗非酒精性脂肪性肝病[J].长春中医药大学学报,2018,34(3):518-521.
    [4] YOUNOSSI ZM,KOENIG AB,ABDELATIF D,et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence,incidence,and outcomes[J]. Hepatology,2016,64(1):73-84.
    [5] ZHU JZ,ZHOU QY,WANG YM,et al. Prevalence of fatty liver disease and the economy in China:A systematic review[J].World J Gastroenterol,2015,21(18):5695-5706.
    [6] WU J,XU H,HE X,et al. Six-year changes in the prevalence of obesity and obesity-related diseases in Northeastern China from 2007 to 2013[J]. Sci Rep,2017,7:41518.
    [7] National Workshop on Fatty Liver and Alcoholic Liver Disease,Chinese Society of Hepatology,Chinese Medical Association;Fatty Liver Expert Committee,Chinese Medical Doctor Association. Guidelines of prevention and treatment for nonalcoholic fatty liver disease:A 2018 uptate[J]. J Clin Hepatol,2018,34(5):947-957.(in Chinese)中华医学会肝病学分会脂肪肝和酒精性肝病学组,中国医师协会脂肪性肝病专家委员会.非酒精性脂肪性肝病防治指南(2018年更新版)[J].临床肝胆病杂志,2018,34(5):947-957.
    [8] YANG XX,WANG X,DONG JC,et al. The association of mitochondrion and the effect of Chinese medicinal herb in nonalcoholic fatty liver disease[J]. Chin Tradit Patent Med,2018,40(8):1799-1804.(in Chinese)杨兴鑫,王曦,董金材,等.线粒体与非酒精性脂肪性肝病关系及中药对其缓解作用的研究进展[J].中成药,2018,40(8):1799-1804.
    [9] IPSEN DH,LYKKESFELDT J,TVEDEN-NYBORG P. Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease[J]. Cell Mol Life Sci,2018,75(18):3313-3327.
    [10] NEUSCHWANDER-TETRI BA. Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis:The central role of nontriglyceride fatty acid metabolites[J]. Hepatology,2010,52(2):774-788.
    [11] LEMASTERS JJ,NIEMINEN AL,QIAN T,et al. The mitochondrial permeability transition in cell death:A common mechanism in necrosis,apoptosis and autophagy[J]. Biochim Biophys Acta,1998,1366(1-2):177-196.
    [12] KOBAYASHI S. Choose delicately and reuse adequately:The newly revealed process of autophagy[J]. Biol Pharm Bull,2015,38(8):1098-1103.
    [13] KIM I,RODRIGUEZ-ENRIQUEZ S,LEMASTERS JJ. Selective degradation of mitochondria by mitophagy[J]. Arch Biochem Biophys,2007,462(2):245-253.
    [14] KLIONSKY DJ,ABDALLA FC,ABELIOVICH H,et al. Guidelines for the use and interpretation of assays for monitoring autophagy[J]. Autophagy,2012,8(4):445-544.
    [15] RODRIGUEZ-ENRIQUEZ S,HE L,LEMASTERS JJ. Role of mitochondrial permeability transition pores in mitochondrial autophagy[J]. Int J Biochem Cell Biol,2004,36(12):2463-2472.
    [16] KIM I,LEMASTERS JJ. Mitochondrial degradation by autophagy(mitophagy)in GFP-LC3 transgenic hepatocytes during nutrient deprivation[J]. Am J Physiol Cell Physiol,2011,300(2):c308-c317.
    [17] XIE R,NGUYEN S,MCKEEHAN WL,et al. Acetylated microtubules are required for fusion of autophagosomes with lysosomes[J]. BMC Cell Biol,2010,11:89.
    [18] WILLIAMS JA,DING WX. A mechanistic review of mitophagy and its role in protection against alcoholic liver disease[J]. Biomolecules,2015,5(4):2619-2642.
    [19] EID N,ITO Y,OTSUKI Y. Triggering of parkin mitochondrial translocation in mitophagy:Implications for liver diseases[J].Front Pharmacol,2016,7:100.
    [20] MEI S,NI HM,MANLEY S,et al. Differential roles of unsaturated and saturated fatty acids on autophagy and apoptosis in hepatocytes[J]. J Pharmacol Exp Ther,2011,339(2):487-498.
    [21] SINGH R,CUERVO AM. Autophagy in the cellular energetic balance[J]. Cell Metab,2011,13(5):495-504.
    [22] SINGH R,KAUSHIK S,WANG YJ,et al. Autophagy regulates lipid metabolism[J]. Nature,2009,458(7242):1131-1135.
    [23] RAUTOU PE,MANSOURI A,LEBREC D,et al. Autophagy in liver diseases[J]. J Hepatol,2010,53(6):1123-1134.
    [24] YIN XM,DING WX,GAO WT. Autophagy in the liver[J].Hepatology,2008,47(5):1773-1785.
    [25] YANG L,LI P,FU S,et al. Defective hepatic autophagy in obesity promotes ER stress and causes insulin resistance[J].Cell Metab,2010,11(6):467-478.
    [26] KOGA H,KAUSHIK S,CUERVO AM. Altered lipid content inhibits autophagic vesicular fusion[J]. FASEB J,2010,24(8):3052-3065.
    [27] AMIR M,CZAJA MJ. Autophagy in nonalcoholic steatohepatitis[J]. Expert Rev Gastroenterol Hepatol,2011,5(2):159-166.
    [28] CSAK T,GANZ M,PESPISA J,et al. Fatty acid and endotoxin activate inflammasomes in mouse hepatocytes that release danger signals to stimulate immune cells[J]. Hepatology,2011,54(1):133-144.
    [29] ZHANG Q,RAOOF M,CHEN Y,et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury[J]. Nature,2010,464(7285):104-107.
    [30] KIM MJ,YOON JH,RYU JH. Mitophagy:A balance regulator of NLRP3 inflammasome activation[J]. BMB Rep,2016,49(10):529-535.
    [31] CHI ZC. Pathogenesis of non-alcoholic fatty liver disease[J]. World Chin J Dig,2017,25(8):670-683.(in Chinese)池肇春.非酒精性脂肪性肝病发病机制研究进展与现状[J].世界华人消化杂志,2017,25(8):670-683.
    [32] YAMAUCHI T,KAMON J,ITO Y,et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects[J]. Nature,2003,423(6941):762-769.
    [33] XU A,WANG Y,KESHAW H,et al. The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice[J]. J Clin Invest,2003,112(1):91-100.
    [34] HARDIE DG. Minireview:The AMP-activated protein kinase cascade:The key sensor of cellular energy status[J]. Endocrinology,2003,144(12):5179-5183.
    [35] LI Z,XU J,ZHENG P,et al. Hawthorn leaf flavonoids alleviate nonalcoholic fatty liver disease by enhancing the adiponectin/AMPK pathway[J]. Int J Clin Exp Med,2015,8(10):17295-17307.
    [36] SLUTSKY N,VATARESCU M,HAIM Y,et al. Decreased adiponectin links elevated adipose tissue autophagy with adipocyte endocrine dysfunction in obesity[J]. Int J Obes(Lond),2016,40(6):912-920.
    [37] GUO R,NAIR S,ZHANG Y,et al. Adiponectin deficiency rescues high-fat diet-induced hepatic injury,apoptosis and autophagy loss despite persistent steatosis[J]. Int J Obes(Lond),2017,41(9):1403-1412.
    [38] EGAN DF,SHACKELFORD DB,MIHAYLOVA MM,et al. Phosphorylation of ULK1(h ATG1)by AMP-activated protein kinase connects energy sensing to mitophagy[J]. Science,2011,331(6016):456-461.
    [39] LIN Z,WU F,LIN S,et al. Adiponectin protects against acetaminophen-induced mitochondrial dysfunction and acute liver injury by promoting autophagy in mice[J]. J Hepatol,2014,61(4):825-831.
    [40] JIANG P,HUANG Z,ZHAO H,et al. Hydrogen peroxide impairs autophagic flux in a cell model of nonalcoholic fatty liver disease[J]. Biochem Biophys Res Commun,2013,433(4):408-414.
    [41] SZABO G,CSAK T. Inflammasomes in liver disease[J]. J Hepatol,2012,57(37):642-654.
    [42] DOGRU T,ERCIN CN,ERDEM G,et al. Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis[J]. Am J Gastroenterol,2008,103(12):3217-3218.
    [43] ASANUMA T,ONO M,KUBOTA K,et al. Super paramagnetic iron oxide MRI shows defective Kupffer cell uptake function in non-alcoholic fatty liver disease[J]. Gut,2010,59(2):258-266.
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  • 收稿日期:  2019-08-01
  • 出版日期:  2019-12-20
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